18-hydroxy-11-deoxycorticosterone was shown to be an endogenous secretory product of the human adrenal cortex by this laboratory and evidence was produced for its hypersecretion in some instances of hyporeninemic hypertension over the past three years. It is the purpose of this proposal to study the physiologic alterations in 18-OH-DOC secretion including circadian variation and negative feedback. In addition, alterations in these regulatory systems will be studied in patients with hyporeninemic hypertension. 18-OH-DOC serves as a precursor of a comparatively new steroid structure, 16 alpha, 18-dihydroxy-11-deoxycorticosterone. Patients with adenomastose adrenal tissue obtained from hyporeninemic hypertensives have shown marked increase and efficiency of 16 alpha-hydroxylation of 18-OH-DOC. Significance of this steroid product in hypertensive disorders can be determined by the development of procedures to quantify intermediary metabolism of this substance. The role of the anterior pituitary and regulation of aldosterone biosynthesis will be examined using the pituitary fractions of Raben in the canine plasma aldosterone responsiveness to these fractions. ACTH will be re-examined in terms of its temporal limitations in stimulation of aldosterone secretion which might be expected to occur through the out-pouring of mineralocorticoids from the zona fasciculata (DOC and 18-OH-DOC) which can indirectly suppress plasma renin activity and hence, diminish angiotensin's permissive stimulation of the adrenal cortex. C-19 free steroids and the steroid ester sulfates will be compared in terms of response to a variety of trophic substances including growth hormone, ACTH and possibly somatomedin. These findings will be related to the common observation of hirsutism and elevated dehydroepiandrosterone sulfate secretion in the adult woman. BIBLIOGRAPHIC REFERENCES: Dale, S. L., Komanicky, P., Pratt, J. H. and Melby, J. C.: Radioimmunoassay of 18-Hydroxy-11-Deoxycorticosterone in Plasma. (In Press), J. C. E. M., 1976. Pratt, J. H., Dale, S.L. and Melby, J. C.: The Effect of Administered ACTH on Aldosterone Metabolism and Secretion. (In Press), J. C. E. M., 1976.